Among optically active compounds there are a lot of very useful compounds as intermediates of drugs, etc. In particular, nitrogen-containing compounds such as optically active nitro compounds or optically active cyano compounds are especially interesting due to wide application fields as synthetic intermediates for drug Rolipram, GABAB receptor agonist Baclofen, immune drug β-methyl carbapenem and the like, and as building blocks for endothlin A antagonist ABT-546 and the like.
Various methods have been developed as synthetic methods for optically active nitro compounds, wherein as to an asymmetric Michael reaction using an asymmetric metal catalyst, reaction making the rhodium complex its catalyst has been reported (J. Am. Chem. Soc. 2000, 122, 10716). Reactions making asymmetric copper complexes as catalysts have also been reported (Tetrahedron Asymmetry 1998, 9, 1341 and J. Am. Chem. Soc. 2003, 125, 3700). Further, reactions making asymmetric magnesium complexes as catalysts have been reported (International publication 00/15599 Pamphlet, U.S. Pat. No. 6,329,536 and J. Am. Chem. Soc. 1999, 121, 10215).
However, since in the method discussed in J. Am. Chem. Soc. 2000, 122, 10716, alkylboronic acid is used as a nucleophile, it is necessary to prepare the alkylboronic acid in advance, and in the reaction there are tedious problems that it is necessary to add the prepared alkylboronic acid in an more amount than an electrophile and further to react in a relatively high temperature, etc. Also, in the methods described in Tetrahedron Asymmetry 1998, 9, 1341 and J. Am. Chem. Soc. 2003, 125, 3700, dialkylzinc unstable in the air is used as a reagent and it is necessary to keep the reaction temperature from −30° C. to −78° C. in order to obtain a relatively high enantioselectivity. Further, in the methods in International publication 00/15599 Pamphlet and U.S. Pat. No. 6,329,536 and in J. Am. Chem. Soc. 1999, 121, 10215, reactions of dicarbonyl compounds with nitroalkenes are investigated, though in order to get Michael adducts in high yield and high selectivity it is necessary to add a relatively high amount of catalyst in about 5 mol % and further to add molecular sieve and an amine as promoter. Based on this, although a magnesium complex alone act as Lewis acid and activates the dicarbonyl compounds, it has no function to fully accelerate deprotonation of the dicarbonyl compounds and is not necessarily an effective catalyst system.
Accordingly, the methods to synthesize these optically active nitro compounds have not necessarily been high in utility because of use of unstable reagents, use of a large catalyst amount, further, necessity of a high temperature or low temperature reaction conditions, and a long time reaction and the like.
Further, as to an optically active cyano compound, of course it itself and also an optically active amine compound obtained by reduction of the cyano group of said compound are extremely important compounds as building blocks for drugs, etc., though its rational synthetic method has not been fully developed yet, and the synthetic method of the optically active cyano compound by Michael reaction has not been known yet.
In the mean time, although reactions to add malonic acid diesters to substrates stereoselectively using a ruthenium catalyst which makes a chiral diamine as ligand have been reported (J. Am. Chem. Soc. 2003, 125, 7508), compounds as a Michael acceptor are only disclosed for cyclic enones such as cyclopentenone, cyclohexenone and cycloheptenone, and therefore, in the reactions only optically active carbonyl compounds are obtained.
Consequently, further development of a rational synthetic method of optically active nitro or cyano compounds, which are interesting for manufacturing drugs, etc., is seriously needed.